O^l-C^-  ^5^5^33"^ 


Issued  September  25, 1912. 


A 

0 

ucso 

U 
1 

JTHE 

0 
8 

— '=^-^ — S 

3I0NAL 

4 
3 

^^1 

2 

1 

7 

U.  S.  DEPARTMENT  OF  AGRICULTURE, 

BUREAU  OF  ANIMAL  INDUSTRY.— Bulletin  153. 

A.  D.  MELVIN,  Chief  of  Bureau. 


HE  ACTION  OF  ANTHELMINTICS  ON  PARASITES 

LOCATED    OUTSIDE   OF  THE 

ALIMENTARY  CANAL. 


BY 


BRAYTON  HOWARD  RANSOM, 

Chief  of  the  Zoological  Division, 
AND 

MAURICE  C.  HALL, 

Assistant  Zoologist,-  Zoological  Division. 


WASHINGTON: 

GOVERNMENT  PRINTING  OFFICE. 

1912. 


Digitized  by  tine  Internet  Arciiive 

in  2Q07  witii  funding  from 

IVIicrosoft  Corporation 


littp://www.arcliive.org/details/actionofantli.elnniOOransiala 


Issaed  September  25, 1912. 

U.  S.  DEPARTMENT  OF  AGRICULTURE, 

BUREAU  OF  ANIMAL  INDUSTRY.— Bulletin  153. 

A.  D.  MELVIN,  Chief  of  Bureau. 


THE  ACTION  OF  ANTHELMINTICS  ON  PARASITES 
LOCATED    OUTSIDE   OF   THE 
■     ALIMENTARY  CANAL. 


BY 


BRAYTON  HOWARD  RANSOM, 

Chief  of  the  Zoological  Division^ 
AND 

MAURICE  C.  HALL, 

Assistant  Zoologist,  Zoological  Division. 


WASHINGTON: 

GOVERNMENT  PRINTING  OFnCE. 

1912. 


THE  BUREAU  OF  ANIMAL  INDUSTRY. 


Chief:  A.  D.  Melvin. 

Assistant  Chief:  A.  M.  FxIRBington. 

Chief  Clerk:  Charles  C.  Carroll. 

Animal  Husbandry  Division:  George  M.  Rommel,  chief. 

Biochemic  Division:  M.  Dorset,  chief. 

Dairy  Division:  B.  H.  Rawl,  chief. 

Field  Inspection  Division:  R.  A.  Ramsay,  chief. 

Meat  Inspection  Division:  Rice  P.  Steddom,  chief. 

Pathological  Division:  John  R.  Mohleb,  chief. 

Quarantine  Division:  Richard  W.  Hickman,  chief. 

Zoological  Division:  B.  H.  Ransom,  chief. 

Experiment  Station:  E.  C.  Schroedeb,  superintendent. 

Editor:  James  M.  Pickens. 

ZOOLOGICAL     DIVISION. 

Chief:  B.  H.  Ransom. 

Assistant   Zoologists:  Albert    Hassall,    Habby    W.    Gbaybill,    Maubice    C. 
Hall,  and  Howabd  Cbawley. 
Junior  Zoologist:  Winthbop  D.  Fosteb. 

2 


LETTER  OF  TRANSMITTAL. 


U.  S.  Department  of  Agriculture, 

Bureau  of  Aj^imal  Industry, 
Washington,  D.  C,  May  2,  1912. 
Sir  :  I  have  the  honor  to  transmit  herewith,  and  to  recommend  for 
publication  as  a  bulletin  of  this  bureau,  a  manuscript  entitled  "  The 
Action  of  Anthelmintics  on  Parasites  Located  Outside  of  the  Ali- 
mentary Canal,"  by  Dr.  B.  H.  Ransom,  Chief  of  the  Zoological  Divi- 
sion, and  Mr.  Maurice  C.  Hall,  assistant  zoologist  in  the  Zoological 
Division  of  this  bureau. 

This  paper  details  the  results  of  some  attempted  medicinal  treat- 
ment of  sheep  for  tapeworm  disease,  and  also  summarizes  our  knowl- 
edge of  the  use  of  anthelmintics  against  parasites  located  outside 
of  the  intestinal  lumen.  While  the  experimental  results  were  nega- 
tive, the  evidence  brought  together  here  indicates  the  need  of  further 
work,  and  this  paper  is  intended  to  simplify  additional  work  by 
furnishing  a  systematic  summary  of  all  previous  work.  It  also  lias 
immediate  practical  utility  as  an  aid  in  judging  the  claims  made  for 
proprietary  medicines. 

Very  respectfully,  A.  D.  Melvix, 

Chief  of  Bureau. 
Hon.  James  Wilson, 

Secretary  of  Agriculture. 

3 


CONTENTS. 


Page. 

Introductory 5 

Historical  review 6 

Somatic  and  extraintestinaJ  tseniasis 6 

Distomatiasis 10 

Autliors'  experiments 16 

General  summary  and  ci'iticism 19 

Bibliography 20 


THE  ACTION  OF  ANTHELMINTICS  ON  PARASITES  LOCATED 
OUTSIDE  OF  THE  ALIMENTARY  CANAL. 


INTRODUCTORY. 

As  commonly  employed,  the  remedies  known  as  anthelmintics  are 
usually  efficacious  preparations.  Their  action  is  based  on  the  prem- 
ises that  they  are  poisons  which  can  be  taken  into  the  digestive  tract 
of  such  animals  as  man,  the  horse,  dog,  or  cat,  in  quantities  not  large 
enough  to  poison  the  host  but  sufficient  to  stupefj'^  or  kill  verminous 
parasites  with  which  they  come  in  contact.  The  parasites  are  usually 
in  the  small  intestine  (intestinal  helminthiasis)  and  occasionally  in 
the  stomach  (gastric  helminthiasis).  In  order  to  avoid  dilution  of 
the  medicine,  and  also  to  give  a  more  effective  contact  with  the  para- 
site, the  patient  is  prepared  in  advance  by  fasting  to  empty  the 
stomach  and  intestine.  Finally  a  purgative  is  administered  to  carry 
out  the  dead  or  stupefied  worms.  All  this  is  comparatively  simple 
And  in  practice  effective. 

Though  anthelmintics  may  be  used  very  successfully  in  treatment 
for  parasites  in  the  stomach  and  small  intestine  of  certain  animals, 
they  are,  as  a  rule,  less  satisfactory  when  applied  to  ruminants.  Medi- 
cines administered  to  ruminants  must  first  pass  the  first,  second,  and 
third  stomachs,  some  or  all  of  which  are  usually  well  filled  with  food 
and  difficult  to  empty  in  any  reasonable  period  of  fasting,  before 
reaching  the  usual  location  of  gastric  parasites,  the  fourth  stomach, 
through  which  in  turn  the  medicines  must  pass  before  they  reach 
the  small  intestine.  In  some  cases,  however,  gastric  and  intestinal 
helminthiasis  in  ruminants  may  be  treated  successfully.  Perroncito 
(1885)^  and  Stiles  (1902),  for  example,  have  reported  satisfactory 
results  from  the  use  of  various  remedies  for  stomach  worms  of  sheep. 
Certain  experiments  have  indicated  that  under  the  right  conditions 
remedies  may  pass  directly  through  the  first  stomach  and  thus  arrive 
more  or  less  promptly  in  the  second  and  following  stomachs  and  the 
intestine.  Powers  (1909),  however,  has  questioned  this,  and  con- 
siders medicinal  treatment  for  stomach  worms  in  ruminants  unsat- 
isfactory. 

As  to  the  treatment  of  parasites  located  in  the  large  intestine,  it 
has  been   found  in   actual   practice,  even   in  animals  with  simple 

*  References  to  literature  will  be  found  In  bibliography  at  end  of  bulletin. 

5 


6  ACTION   OF  ANTHELMINTICS   ON   PARASITES. 

stomachs  and  short  alimentary  tracts,  such  as  the  dog,  that  the  results 
from  the  administration  of  remedies  per  orem  are  generally  very 
unsatisfactory.  Stiles  and  Pfender  (1902),  for  instance,  found  that 
thymol,  a  classic  remedy  for  hookworms,  was  without  effect  on  whip- 
worms of  the  cecum  of  the  dog.  On  the  other  hand,  Miller  (1904) 
claims  to  have  succeeded  in  removing  whipworms  from  the  dog  by 
the  use  of  oleoresin  of  male  fern.  Parasites  located  in  the  large 
intestine  are,  however,  difficult  to  reach  with  ordinary  anthelmintics 
administered  by  mouth. 

In  view  of  the  difficulty  of  reaching  parasites  located  in  the  ali- 
mentary tract  beyond  the  stomach  or  small  intestine,  or  even  in  these 
organs  in  ruminants,  by  means  of  anthelmintics  administered  through 
the  mouth,  it  would  seem  on  first  thought  that  treatment  with  such 
remedies  for  worms  in  the  liver,  pancreas,  muscles,  brain,  blood,  or  in 
other  locations  outside  the  direct  course  of  the  digestive  tract,  would 
be  certain  to  result  unsuccessfully.  Nevertheless  several  more  or  less 
commonly  used  anthelmintics  have  received  favorable  consideration' 
in  the  treatment  of  verminous  parasites  located  outside  the  lumen  of 
the  stomach  and  intestine,  and  the  results  of  the  tests  made  in  some 
cases  apparently  afford  a  basis  for  a  belief  in  their  efficacy. 

HISTORICAL  REVIEW. 

A  consideration  of  the  work  done  on  this  subject  shows  that 
writers,  in  general,  have  recognized  two  lines  of  work:  First,  the 
treatment  of  somatic  and  extraintestinal  tseniasis  where  parasites 
are  located  in  the  brain,  muscles,  liver,  or  subcutaneous  tissue;  and 
second,  the  treatment  of  certain  forms  of  distomatiasis,  where  the 
parasites  are  located  in  the  liver  or  blood.  Parasites  in  the  liver  are, 
of  course,  relatively  nearer  the  usual  site  of  operation  of  anthel- 
mintics. To  the  first  line  of  work  we  wish  to  add  some  notes  on  the 
treatment  of  tseniasis  where  the  parasites  are  located  in  the  liver  and 
in  the  pancreatic  and  bile  ducts.  In  this  case  the  parasite,  Thysano- 
soma  actinioides,  is  also  an  intestinal  parasite,  and  we  use,  therefore, 
the  terms  extraintestinal  and  intestinal  thysanosomiasis  to  indicate 
the  two  forms  of  infestation  with  the  adult  worm. 

Since  writers  along  either  of  the  two  lines  mentioned  have  usually 
confined  their  abstracts  and  criticism  of  related  work  to  work  along 
the  one  line,  this  review  will  summarize  the  two  lines  of  work 
separately. 

SOMATIC  AND  EXTRAINTESTINAL  TiENIASIS. 

Ziirn  (1882a)  states  that  after  trying  for  24  years  to  find  some 
medication  that  would  cure  gid  in  sheep,  he  has  concluded  that  suc- 
cessful treatment  of  the  sort  is  impossible,  and  cautions  against  the 
administration  of  poisons,  which,  in  his  opinion,  results  in  nothing 


HISTORICAL  REVIEW.  7 

but  a  waste  of  time  and  money.  It  is  unfortunate  that  he  did  not 
give  his  experiments  in  detail,  or  at  least  name  the  remedies  he 
tried;  but  from  the  fact  that  he  speaks  of  them  as  poisons  it  seems 
reasonable  to  suppose  that  he  tested  the  various  common  anthelmin- 
tics, all  of  which  are  poisons. 

Curtice  (1889a  and  1890c)  records  tests  of  various  remedies  in 
intestinal  and  extraintestinal  thysanosomiasis  of  sheep,  and  says: 

Various  tseniafuges  were  tried  with  little  success.  The  powdered  prepara- 
tions of  pumpliin  seed,  pomegi"anate-root  bark,  lioosoo,  l^amala,  male  fern,  and 
worm  seed  proved  of  no  avail.  *  *  *  The  presence  of  taeniae  in  the  biliary 
ducts  is  another  reason  why  tseniafuges  can  not  be  entirely  successful  in  treat- 
ment of  sheep  with  T.  fimbriata  [Th.  actinioides].  Any  medicine  which  would 
affect  the  taeniae  in  these  ducts  would  also  affect  the  sheep  seriously.  It  is 
doubtful  whether  they  can  be  killed  or  driven  from  the  ducts. 

Feletti  (1894c)  administered  ethereal  extract  of  male  fern  in  three 
cases  of  .human  cysticercosis,  as  follows: 

1.  Patient  had  had  Taenia  solium.  Present  symptoms:  Convulsions,  cepha- 
lalgia, vertigo,  vomiting.  Small  subcutaneous  nodules  appeared  and  grew  to 
the  size  of  olives ;  one  of  these  was  excised  and  found  to  be  Cysticercus  cellu- 
losae.  No  cestodc  proglottids  or  eggs  were  found  on  fecal  examination.  Feletti 
administered  1  to  3  grams  of  extract  of  male  fern  per  diem  to  the  patient  until 
he  had  given  18  grams.  The  patient  could  not  stand  more.  The  cysticercl 
diminished  to  the  size  of  a  wheat  grain,  but  the  cerebral  trouble  did  not  Im- 
prove, and  the  man  died  a  month  later.    No  autopsy  was  permitted. 

2.  Patient  had  34  subcutaneous  nodules.  One  of  these  was  excised  and  found 
to  be  Cysticercus  ccllulosce.  No  cestode  proglottids  or  eggs  found  on  fecal 
examination.  Feletti  at  first  administered  1  to  1.5  grams  of  extract  of  male 
fern  per  diem,  but  this  was  not  supported  and  the  dose  was  accordingly  cut 
down  to  40  centigrams.  The  total  amount  administered  was  26.5  grams.  The 
nodules  diminished  until  they  could  not  be  felt. 

3.  Patient  had  had  a  tapeworm  three  years  before  and  had  not  recovered 
the  head  in  several  attempts  at  removal.  Present  symptoms :  Convulsions, 
vertigo,  and  vomiting.  For  this  he  was  treated  with  sodium  and  potassium 
bromld.  Seven  nodules  developed.  One  of  these  was  excised  and  found  to 
be  a  cysticercus.  Feletti  administered  60  centigrams  of  extract  of  male  fern 
per  diem,  and  In  a  month  the  nodules  had  disappeared.  The  nervous  condition 
was  Improved,  but  the  trouble  subsequently  recurred  and  was  treated  with 
bromids  with  good  results.  Feletti  thinks  the  recurrence  was  due  to  brain 
alterations,  but  considers  that  the  cysticercl  were  dead. 

According  to  Feletti,  these  cases  demonstrate  that  extract  of  male 
fern  kills  subcutaneous  and  muscular  cysticercl  and  that  it  probably 
acts  upon  cerebral  cysticercl  also.  He  advises  a  dose  of  30  to  40 
centigrams  per  diem  for  30  or  40  days. 

De  Renzi  (1908)  renewed  the  interest  in  this  line  of  work  by  his 
report  of  the  administration  of  extract  of  male  fern  in  four  cases  of 
human  somatic  taeniasis.  "We  quote  the  following  abstract  of  De 
Renzi's  cases  from  Hall  (1909)  : 

1.  The  patient  had  occasion  to  eat  badly  cooked  pork  and  uncooked  sausage; 
had  an  infection  with  Twnia  solium  five  years  previous;  had  attacks  of  con- 


8  ACTION   OF  ANTHELMINTICS   ON   PAKASITES. 

vulsions  and  insensibility  three  years  later,  and  on  treatment  with  a  vermifuge 
had  passed  a  tapeworm  with  the  head.  Two  months  later  the  patient  had 
stronger  convulsions,*  dizziness,  and  shortness  of  breath  on  slight  exertion. 
About  this  time  growths  appeared  on  the  temples  and  the  sternocleido- 
mastoideus.  Five  months  later  the  patient  had  three  cramp-like  attacks  in 
one  day,  followed  by  great  exhaustion.  At  this  time  the  patient  came  to  De 
Kenzi,  who  found  small  swellings  over  the  entire  body  and  great  nervous  de- 
pression. On  the  history  given  here  he  diagnosed  cysticercus  of  the  brain  and 
skin.  After  a  year's  ambulant  treatment  with  male  fern  the  nervous  trouble 
had  disappeared,  so  had  the  swellings,  with  the  exception  of  one  over  the  left 
temple,  and  this  was  removed  by  operation  and  showed  the  presence  of  a 
cysticercus.  The  eosinophilia  present  at  the  beginning  of  the  treatment  had 
disappeared. 

2.  The  second  patient,  a  woman,  had  an  infection  with  Twnia  solium  three 
years  before.  For  two  years  previous  to  treatment  she  had  suffered  from 
dizziness,  headache,  weak  memory,  polyuria,  and  weakness.  A  swelling  over 
the  manubrium  sterni  showed  all  the  claaracteristics  of  a  cysticercus.  After  a 
week's  treatment  the  nervous  symptoms  had  disappeared  and  the  swelling  was 
reduced  to  one-third  its  original  volume.  A  microscopic  examination  of  the 
swelling  was  made,  but  De  Renzi  states  that  in  this  examination  nothing  of 
special  importance  was  noted. 

3.  In  De  Renzi's  third  case  there  was  a  history  of  increasing  pain  in  the 
hypochondrium  for  20  months,  no  fever  or  emaciation,  increase  in  the  area  of 
liver  dullness,  eosinophilia  present,  urine  normal.  The  case  was  diagnosed  as 
hepatic  echinococcosis,  and  all  symptoms  disappeared  under  treatment  in  20 
days.     *     *     *     Fecal  examination  did  not  show  parasites  or  their  eggs. 

4.  The  fourth  patient  was  a  woman  who  had  suffered  for  a  year  with  a  pain 
in  the  thorax  and  often  ctfughed  blood.  In  the  absence  of  tubercular  symptoms 
and  because  the  patient  coughed  up  membranes,  "  Hiiutchen,"  a  diagnosis  of 
lung  echinococcosis  was  made  by  De  Renzi  and  confirmed  by  two  associates. 
In  the  brief  period  of  six  days  she  was  cured  by  male  fern. 

Dianoux  (1909)  has  recorded  a  case  in  which  ocular  and  subcu- 
taneous cysticercosis,  possibly  complicated  by  cerebral  cysticercosis, 
was  apparently  cured  by  the  administration  of  male  fern. 

Before  coming  under  Dianoux's  care,  March  25,  the  patient  had  had  several 
epileptiform  attacks,  and  had  nearly  lost  the  sight  of  the  left  eye.  Examination 
with  the  ophthf-lmoscope  showed  the  presence  of  a  cysticercus  in  the  vitreous 
humor,  and  some  weeks  later  a  nodule,  presumably  a  cysticercus,  was  found 
beneath  the  skin  of  the  groin.  After  treatment  with  male  fern  and  calomel  the 
patient  passed  4  or  5  meters  of  tapeworm  {Twnia  solium).  May  2  the  patient 
experienced  an  epileptifoim  convulsion.  From  May  3  to  20  the  patient  took  2 
grams  of  extract  of  male  fern  per  day ;  treatment  was  then  suspended  a  few 
days.  On  May  24  a  slight  epileptiform  attack  occurred.  Examination  with  the 
ophthalmoscope  showed  that  the  cysticercus  had  become  shriveled  and  motion- 
less. From  May  2.^5  to  June  5,  2  grams  of  extract  of  male  fern  per  day  were 
administered.  June  12  the  cyst  in  the  groin  was  discovered.  June  16  an  epi- 
leptiform attack  occurred,  lasting  15  minutes,  and  the  following  day  there  was 
another  attack.  Treatment  was  resumed.  July  2  treatment  was  suspended; 
the  cyst  had  disappeared  from  the  gi-oin ;  the  general  health  of  the  patient  was 
excellent.  During  10  days  in  August  the  patient  was  given  1.5  grams  of  extract 
of  male  fern  per  day.  November  15  the  patient  was  discharged  as  cured.  The 
cysticercus  had  entirely  disappeared  from  the  eye.  The  only  evidence  of  its 
former  presence  was  a  cicatrice  and  vascular  condition  of  the  retina  at  the 


HISTORICAL  REVIEW.  9 

point  where  the  parasite  had  been  located.  Altogether  102  grams  of  extract  of 
male  fern  had  been  administered  during  a  period  of  71  days,  ftnd  presuniably 
as  a  result  of  this  treatment  a  cysticercus  of  the  eye,  one  under  the  skin  of  the 
groin,  and  probably  others  in  the  motor  centers  of  the  brain,  had  degenerated 
and  become  absorbed.  Dianoux  concludes  that  male  fern  destroys  cysticerci 
because  of  some  selective  action  against  these  parasites. 

Eailliet  in  his  abstract  of  De  Renzi's  article  (De  Renzi,  1909)  has 
noted  that  it  would  be  interesting  to  test  male  fern  on  domestic 
animals  suffering  from  parasitic  diseases  of  the  muscles  and  viscera, 
and  mentions  gid  as  one  disease  in  which  this  treatment  should  be 
attempted.  Such  treatment  was  attempted  and  reported  by  Hall 
(1909).    The  treatment  was  tried  on  three  sheep  as  follows:     t^Kf'*^'^ 

1.  Sheep  showed  characteristic  symptoms  of  gid.  Fifty  grams  of  male  fern 
powder  administered  on  two  consecutive  days.  The  third  day  the  attendant 
accidentally  got  the  dose  in  the  windpipe  of  the  sheep,  killing  the  animal. 
Post-mortem  examination  showed  a  large  living  coenurus  in  the  cerebrum.         ( 

2.  Sheep  showed  pronounced  symptoms  of  gid.  Ethereal  extract  of  male 
fern  administered  in  5  c.  c.  doses  on  27  days  between  April  22  and  May  30,  a 
total  of  135  c.  c.  Sheep  found  dead  May  30,  following  a  gradual  increase  in 
unfavorable  symptoms  from  May  1.  Post-mortem  examination  showed  a  large 
living  coenurus  in  the  cerebrum. 

3.  Sheep  showed  characteristic  symptoms  of  gid.  Ethereal  extract  of  male 
fern  administered  in  5  c.  c.  doses  on  consecutive  days,  with  the  exception  of 
one  day,  until  a  total  of  45  c.  c.  had  been  given.  No  improvement  in  condi- 
tion. Treatment  discontinued  and  sheep  found  dead  four  days  later.  Post- 
mortem examination  of  the  brain  showed  a  small  live  coenurus. 

Hall  has  given  a  critical  review  of  De  Renzi's  cases,  and  concludes 
that  they  are  open  to  suspicion  of  error  as  regards  diagnosis  and  the 
connection  between  the  disease,  the  treatment,  and  the  cure. 

Moussu  (1910)  has  also  reported  some  tests  of  ethereal  extract  of 
male  fern  administered  for  two  months  to  two  giddy  sheep.  There 
was  a  marked  amelioration  of  symptoms,  but  at  the  autopsy,  two 
months  after  the  cessation  of  treatment,  there  was  a  coenurus  in  the 
brain  of  each,  very  large  in  one  case  and  the  size  of  a  hazelnut  in 
the  other,  and  neither  of  them  degenerated.  Moussu  also  tested  the 
treatment  on  a  pig  affected  with  cysticercosis  which  had  been  devel- 
oping for  more  than  six  months,  the  vesicles  being  readily  visible 
under  the  tongue  and  the  conjunctiva.  The  condition  of  the  pig, 
instead  of  improving,  became  worse  from  day  to  day. 

In  view  of  the  conflict  between  his  results  and  those  obtained  by 
De  Renzi  and  Dianoux,  Moussu  concludes  that  the  influence  of  male 
fern  only  makes  itself  felt  on  young  lesions  and  those  in  course  of 
development,  but  that  where  the  cysts  are  entirely  developed  the 
medicament  remains  entirely  without  effect. 

The  most  recent  publislied  work  upon  this  subject  available  to  us 
is  that  of  Deve  (1911).    His  test  of  the  treatment  was  as  follows: 

Three  rabbits  were  given  a  snt)cutaneou8  injection  of  brood  capsules  from  a 
iydatid  cyst.  No.  1  was  kept  as  a  check.  No.  2  was  given  each  day  for  52 
50CG4"'— Bull.  15.3—12 2 


^0  .         ACTION   OF   ANTHELMINTICS   ON   PARASITES. 

days  4.5  c.  c.  of  ethereal  extract  of  male  fern.  The  weight  of  the  rabbit  was 
2.9  grams.  No.  3,  weighing  the  same,  was  given  9  c.  c,  or  6  c.  c,  per  kilogram, 
or  double  the  corresponding  dose  for  man.  The  treatment  was  begun  the  same 
day  as  the  injection.  Five  months  later  normal  live  echinococcus  cysts  were 
found  in  all  three  rabbits.  From  this  Dev6  concludes  that  in  doses  as  large 
or  twice  as  large  as  De  Reuzi  used  and  extending  over  a  much  greater  length 
of  time  the  male  fern  was  without  effect  on  the  hydatid  cysts.  The  treatment 
showed  itself  incapable  of  affecting  the  delicate  metamorphosis  of  the  scolex, 
an  initial  phase  in  which  it  seems  that  the  parasite  would  be  especially  vul- 
nerable. Male  fern  is  therefore  provisionally  deemed  inefficacious  in  hydatid 
disease. 

Deve  notes  that  his  results  in  echinococcosis  are  in  agreement 
with  the  negative  results  obtained  by  Hall  in  cysticercosis  (Deve's 
error;  Hall's  cases  dealt  with  coenurus,  as  noted  above),  by  Moussu 
in  ccenurosis,  and  finally  with  the  very  unsatisfactory  results  ob- 
tained by  Railliet,  Moussu,  and  Henry  in  distomatiasis. 

A  summary  of  the  foregoing  indicates  that  results  following  the 
administration  of  male  fern  were  claimed  as  follows : 

Successful  in  6  cases  of  human  cysticercosis  (4  subcutaneous,  1 
subcutaneous  and  cerebral,  and  1  subcutaneous  and  ocular),  and  in  2 
cases  of  human  echinococcosis  (1  hepatic  and  1  pulmonary)  ;  a  total 
of  8  cases  of  Imman  somatic  tseniasis. 

Unsuccessful  in  5  cases  of  ovine  cerebral  ccenurosis,  2  cases  of 
leporine  general  echinococcosis,  and  1  case  of  porcine  muscular  and 
ocular  cysticercosis;  a  total  of  8  cases  of  somatic  tseniasis  in  lower 
animals. 

A  critical  discussion  of  these  cases  will  be  given  later.  It  is  suffi- 
cient at  this  point  to  note  that  all  tests  on  man  were  claimed  to  be 
successful  and  that  all  experiments  on  animals  were  failures.  The 
cases  of  Ziirn  and  Curtice  are  too  indefinite  to  include  in  this  sum- 
mary. 

DISTOMATIASIS. 

Under  this  heading  hepatic  distomatiasis  will  be  considered  first 
and  venal  distomatiasis  second. 

Grassi  and  Calandruccio  (1884  and  1885)  record  the  first  cases  of 
which  we  are  aware  where  extract  of  male  fern  was  used  in  dis- 
tomatiasis. The  article  published  in  1884  is  not  available  to  us, 
but  from  the  article  of  the  following  year  it  appears  that  they  ad- 
ministered to  sheep  a  single  dose  consisting  of  5  grams  of  ethereal 
extract  of  male  fern  in  50  grams  of  ethereal  tincture  of  male  fern. 
They  .note  that  one  might  use  injections  of  male  fern,  but  that  it 
would  not  always  be  necessary.  The  injection  should  consist  of  1 
gram  of  the  ethereal  extract  mixed  with  1  gram  of  the  tincture  and 
injected  directly  into  the  liver  by  means  of  a  Pravaz  syringe.  A 
postscript,  based  on  later  work,  adds  that  this  injection  should  not 


HISTORICAL  REVIEW.  11 

be  employed.  They  find  that  for  24  to  48  hours  after  the  adminis- 
tration of  tlie  medicine  the  feces  contained  numerous  flukes  and 
nematodes.  After  three  days  the  feces  show  no  eggs,  and  on  autopsy 
D£>  flukes  or  strongyles  are  found.  The  number  of  tests  and  other 
details  are  not  given. 

They  point  out  that  this  remedy  should  be  tried  in  human  dis- 
tomatiasis,  and  that  the  injection  method  might  be  useful  in  echino- 
coccus  infections. 

Perroncito  (1886)  has  repeated  the  experiments  of  Grassi  and 
Calandruccio  and  reports  favorably  on  the  use  of  male  fern,  noting, 
however,  certain  unfavorable  results  from  its  use.  His  experiments 
were  as  follows: 

1.  Sheep  with  symptoms  of  fluke  disease.  Fecal  examination  showed  two 
to  three  eggs  of  Strongyliis,  probably  8.  cotitoi'tvs,  and  three  to  four  fluke  eggs 
per  slide.  Administered  10  grams  of  ethereal  extract  of  male  fern  in  48  grams 
of  ethereal  tincture.  The  animal  became  tympanic,  due  to  ethereal  vapor  de- 
veloped in  the  stomach,  and  in  a  few  minutes  fell  as  if  struck  dead.  After  40 
minutes  rose.  At  the  end  of  2  hours  it  had  recovered  from  the  symptoms  of 
anesthesia  and  other  phenomena  of  etherization.  Some  weeks  later  the  feces 
showed  one  strongyle  egg  and  one  distome  egg  per  slide. 

2.  Administered  to  sheep  affected  with  liver  fluke,  5  grams  of  ethereal  extract 
of  male  fern  in  50  grams  of  the  tincture.  Usual  symptoms  of  flatulence  and 
defecation.  After  30  to  40  minutes  sheep  gradually  returned  to  normal  condi- 
tion. Examination  of  the  feces  showed  numerous  distome  and  strongyle  eggs. 
Two  days  later  examination  showed  distome  and  hookworm  eggs,  but  notice- 
ably diminished  in  number.  There  had  been  10  to  12  eggs  per  slide ;  there  were 
now  4  to  5. 

Two  days  later  repeated  the  dose,  substituting  6  grams  of  ethereal  extract 
in  place  of  5  grams.  The  animal  showed  more  severe  symptoms  than  on  the 
first  occasion.    There  was  considerable  flatulence  at  the  end  of  an  hour. 

Feces  collected  40  hours  after  the  second  dose  of  male  fern  showed  2  to  3 
distome  eggs  per  slide.  •  Animal  seemed  much  improved.  Seven  days  after  the 
second  dose  the  feces  showed  only  one  distome  egg  to  three  or  four  slides. 

3.  A  sheep  infested  with  a  large  number  of  liver  flukes,  about  800,  was  given 
a  large  dose  of  male  fern  and  died  iu  10  or  12  hours.  Autopsy  showed  that 
the  flukes  were  apparently  all  dead. 

This  last  case  had  been  previously  published  by  Perroncito  (1885). 

The  next  article  dealing  with  experimental  medication  of  hepatic 
distomatiasis  which  has  come  to  our  attention  is  that  of  Romagnoli 
(1903),  who  claims  to  have  had  good  results  in  the  treatment  of  dis- 
tomatiasis in  sheep  from  the  daily  administration  of  1  grain  of  salol 
in  a  teaspoonful  of  water  for  8  days.  According  to  that  author  the 
salol  kills  the  cercarise  which  are  still  in  the  stomach  and  thus  pre- 
vents further  infestation,  so  that  if  the  sheep  are  meanwhile  given 
plenty  of  nourishment  they  rapidly  recover  their  health  and  finally 
become  completely  cured.  Romagnoli's  treatment  is  of  a  different 
character  from  that  reported  by  other  writers  in  that  it  is  supposed 


12  ACTION   OF  ANTHELMINTICS   ON   PARASITES. 

to  act  upon  jDarasites  during  their  invasion  of  the  body  and  not  upon 
those  which  have  alread}"  become  established  in  the  host 

Floris  (1907,  1908)  has  used  carbon  bisulphid,  a  remedy  which 
Perroncito  and  Bosso  (1894)  and  Wessel  (1901)  had  reported  as 
efficacious  against  Gastro'plnliis  in  the  horse,  and  which  Taar  (1907) 
had  found  efficacious  against  Gastroph'dus  and  Ascaris  in  the  horse. 
Floris  administered  the  carbon  bisulphid  in  gelatin  capsules  in  doses 
of  10  to- 15  grams  three  or  four  times  a  week.  The  treatment  was  not 
attended  by  unpleasant  effects  and  served  to  free  the  animals  of 
flukes,  the  feces  containing  5  to  10  flukes  at  a  time.  Floris  notes  that 
this  is  a  very  inexpensive  remedy. 

Alessandrini  (1908)  reports  that  he  had  administered  extract  of 
male  fern  to  two  sheep  which  were  severely  infested.  The  sheep  were 
dead  two  days  later.  Autopsy  showed  the  flukes  in  the  intestine  and 
liver  to  be  dead  and  degenerated. 

Pericaud  (1908)  has  a  rather  glowing  account  of  the  virtues  of  a 
so-called  "  distomasine,"  said  to  consist  of  a  glucosid  and  some  plant 
essence.  He  gives  no  experimental  tests,  and  the  paper  apparently 
adds  nothing  to  our  knowledge. 

Borini  (1911)  states  that  in  1905,  at  the  suggestion  of  Perroncito, 
ethereal  extract  of  male  fern  was  used  to  arrest  a  plague  of  bovine 
distomatiasis  occurring  on  the  estate  of  a  rich  proprietor  in  Calabria. 
Experiments  have  been  made  on  laboratory  animals  from  that  year 
on,  the  treatment  being  especially  tested  on  sheep.  These  experi- 
ments, according  to  Borini,  confirm  tlie  therapeutic  value  of  male 
fern  against  distomatiasis.  In  light  infections  cures  were  always 
obtained;  in  the  worst  cases  of  advanced  cachexia  the  treatment 
failed.  The  use  of  thymol  in  connection  with  male  fern  is  recom- 
mended. 

Railliet,  Moussu,  and  Henry  (1911)  have  recently  published  a 
series  of  articles  on  the  treatment  of  distomatiasis.  In  their  first 
papers  (1911a  and  1911b)  they  note  the  desirability  of  some  medica- 
tion in  view  of  the  considerable  losses  suffered  in  France  in  1910. 
They  first  experimented  with  medicines^  Avhich  maj?^  be  eliminated 
by  the  liver,  especially  aloes,  calomel,  sodium  salicylate,  and  "boldo." 
Most  of  the  animals  treated  with  these  remedies  improved,  but  there 
was  no  cure,  no  destruction  of  the  parasites.  Autopsy  showed  the 
flukes  to  be  still  alive  after  treatment  extending  over  15  days  to 
three  weeks.  It  seemed  as  though  the  treatment  reduced  the  activity 
of  the  flukes  without  really  having  a  specific  effect  on  them. 

In  another  series  of  experiments  they  used  compounds  of  phos- 
phorus, arsenic,  and  mercury-,  as  phosphorated  oil,  arsenic,  atoxyl, 
arseno-benzol,  trypanblau,  benzoate  of  mercury,  and  fluid  extract  of 
broom.     None  of  them  gave  certain,  jjositive  results. 


HISTORICAL  REVIEW.  1^ 

In  a  third  paper  (Eailliet,  Moussu,  and  Henry^  1911c)  these 
authors  report  better  success  in  their  tests  of  a  new  series  of  sub- 
stances, including  particular^  tartar  emetic,  urotropin,  atoxyl,  and 
ethereal  extract  of  male  fern. 

The  sheep  used  were  for  the  most  part  heavily  infested  and  had 
an  intense  cirrhosis  and  often  a  perforation  of  the  capsule  of  Glis- 
son,  the  flukes  which  caused  the  perforation  escaping  to  the  peri- 
toneal cavity.  Many  had  a  mixed  infection  with  Fasciola  hepatica 
and  Dicrocmlium  lanceatum. 

Tartar  emetic  and  urotropin  proved  to  be  inefficacious.  Atoxyl 
produced  the  evacuation  of  degenerated  F.  hepatica  in  one  heifer. 

The  tests  with  ethereal  extract  of  male  fern  were  more  satisfac- 
tory. An  abstract  is  given  of  Alessandrini's  (1908)  experiments  with 
male  fern,  noting  this  as  the  only  work  of  the  sort  of  which  they 
were  aware.  Their  own  tests  were  made  on  five  sheep,  three  others 
being  kept  as  checks.  The  sheep  were  given  5  grams  of  ethereal 
extract  in  25  c.  c.  of  oil.  Autopsy  was  made  immediately  after 
death.    The  experiments  are  as  follows : 

1.  Sheep  received  one  dose  and  died  12  hours  later.  Three  hundred  and 
ninety  F.  hepatica  and  numerous  D.  Janccatum  in  liver;  all  alive. 

2.  Sheep  received  two  doses  at  16-hour  intervals  and  was  killed  in  extremis 
24  hours  after  the  second  dose.  The  biliary  canals  contained  numerous  live 
D.  lanceatum  and  55  F.  hepatica,  4  of  them  being  alive  and  the  rest  degen- 
erated and  of  a  yellowish-green  color.  The  gall  bladder  contained  142  F. 
hepatica,  all  dead,  though  only  3  showed  the  same  alteration  as  the  preceding. 
The  small  intestine  contained  16  degenerated  specimens  and  the  large  intestine 
contained  10  dead  but  not  degenerated  specimens. 

3.  Sheep  received  three  doses  at  16  and  24  hour  intervals.  Killed  3  days 
after  the  last  dose.  Biliary  canals  contained  several  live  D.  lanceatum. 
There  were  9  F.  hepatica,  all  degenerated,  in  the  gall  bladder,  but  none  in  the 
biliary  canals  or  in  the  intestine. 

4.  Sheep  received  four  doses  at  24,  24,  and  48  hour  intervals.  Died  7  hours 
after  the  last  dose.  Biliary  canals  contained  numerous  live  D.  lanceatum. 
There  were  5  degenerated  F.  hepatica  in  the  gall  bladder,  none  in  the  biliary 
canal,  1  degenerated  specimen  in  the  large  intestine,  and  about  50  live  speci- 
mens in  the  peritoneal  cavity,  associated  with  peritonitis. 

5.  Sheep  received  four  doses  at  48,  24,  and  24  hour  intervals.  Killed  3  days 
after  the  last  dose.  Biliary  canals  contained  several  D.  lanceatum,  all  living. 
There  were  no  /•'.  hepatica  in  the  bile  ducts,  the  gall  bladder,  or  the  intestine. 

The  three  check  sheep  were  killed  at  the  end  of  the  experiment  and  showed 
178,  85,  and  497  F.  hepatica,  respectively,  and  numerous  D.  lanceatum,  all 
living. 

The  degeneration  undergone  by  F.  hepatica  under  the  influence  of  male 
fern,  and  to  a  lesser  extent  of  atoxyl,  begins  at  (he  posterior  extremity  and 
progresses  anteriorly,  some  Individuals  being  green  and  flabby  at  the  posterior 
end,  while  the  cephalic  end  was  still  capable  of  movement. 

They  conclude  that  male  fern  is  a  satisfactory  treatment  for  in- 
fection with  F.  hepatica  if  taken  before  there  are  irremediable 
lesions  and  at  least  four  doses  of  5  grams  each  administered.    This 


14  ACTION   OF   ANTHELMINTICS   ON   PARASITES. 

will  kill  F.  hepatica  in  the  liver,  but  not  in  the  peritoneal  cavity. 
At  the  same  time  it  is  effective  against  gastrointestinal  strongylosis. 
It  has  no  effect  on  D.  larweatum. 

In  a  later  paper  (Railliet,  Moussu,  and  Henry,  1911d)  these 
authors  recapitulate  the  foregoing,  noting  the  earlier  work  of 
Grassi  and  Calandruccio  and  of  Perroncito.  They  add  the  following 
experiments : 

Four  sheep  were  given  5  grams  of  ethereal  extract  of  male  fern  in  25  c.  c.  of 
oil  for  four  successive  days,  a  fifth  animal  being  kept  as  check.  All  the  sheep 
showed  fluke  eggs  in  the  feces.  Four  days  after  the  last  dose  they  were  all 
killed.    Autopsy  showed  the  following : 

1.  Liver  contained  1  F.  hepatica  (presumably  alive),  but  marked  lesions  of 
cirrhosis  indicated  the  recent  disappearance  of  other  flukes. 

2.  Liver  contained  2  live  F.  hepatica  in  the  terminal  ducts  and  3  dead 
and  degenerated  forms.    Hepatic  lesions  moderated. 

3.  Liver,  abnormal  in  appearance,  contained  26  live  F.  hepatica  and  1 
dead  one. 

4.  Liver  contained  1  live  F.  hepatica. 

5.  Check  animal.    Liver  strongly  cirrhotic,  contained  296  live  F.  hepatica. 
All  animals  contained  a  number  of  live  D.  lanceatum. 

They  conclude  that  male  fern  is  effective,  and,  for  sheep,  suggest 
a  dose  of  1  gram  of  ethereal  extract  for  every  5  kilos  of  live  weight  of 
animal ;  for  cattle,  about  30  grams  for  350  to  400  kilos  of  live  weight. 
They  note  that  male  fern  is  comparatively  cheap  and  suggest  that  it 
be  administered  by  means  of  a  rubber  tube. 

The  status  of  anthelmintics  in  bilharziasis  is  indicated  in  the 
following  summary: 

Stiles  (1904)  says:  "Favorable  results  are  claimed  from  repeated 
doses  of  male  fern ;  some  authors  consider  specific  treatment  futile." 

Sandwith  (1909)  writes  of  bilharziasis : 

No  method  has  as  yet  been  discovered  of  killing  the  worms  in  the  human 
body;  the  ordinary  vermifuges  are  useless.  *  *  *  The  liquid  extract  of 
male  fern,  in  doses  of  15  minims  3  times  a  day,  is  the  only  drug  of  known  value, 
for,  though  it  does  not  expel  the  parasites  [How  could  it?],  it  seems  to  weaken 
their  power  of  doing  harm ;  it  diminishes  hematuria,  allays  vesical  irritation, 
and  reduces  the  number  of  eggs  passed  in  the  urine  and  feces. 

Joannides  (1911)  has  tried  salvarsan  in  bilharziasis  in  8  cases,  and 
reports  that  a  single  injection  of  0.5  to  0.6  gram  (?)  of  salvarsan 
in  the  case  of  adults  and  0.25  gram  (?)  in  the  case  of  a  12-year-old 
child  resulted  in  cessation  or  great  diminution  of  hematuria,  relief 
from  vesical  and  urethral  irritation,  and  a  disappearance  of  the  eggs 
from  the  urine.  He  concludes  that  salvarsan  is  destructive  of  Schis- 
tosomum  hcematohium  and  its  eggs  and  thus  brings  about  a  cure  of 
the  disease. 

Looss  (1912)  takes  exception  to  the  conclusions  of  Joannides  and 
states  that  bilharziasis  is  a  disease  characterized  by  lesions  due  to  the 
passage  through  or  retention  in  the  tissues  of  the  bladder,  rectum, 


HISTORICAL  REVIEW.  15 

etc.,  of  vast  numbers  of  eggs,  the  parasite  itself  in  the  blood  vessels 
having  practically  no  direct  pathological  significance.  By  the  time 
the  patient  goes  to  a  physician  for  treatment  for  hematuria  the 
worms  producing  the  eggs  which  cause  this  are  probably  dead  or 
near  their  end,  Looss  looks  upon  the  cures  reported  by  Joannides 
as  resulting  from  an  artificial  retention  of  the  eggs  in  the  tissues, 
causing  thereby  a  suppression  of  the  symptoms  but  not  a  cure  of  the 
disease.  For  the  purpose  of  this  article — a  consideration  of  the 
question  whether  anthelmintics  are  effective  against  metazoan  para- 
sites located  elsewhere  than  in  the  digestive  tract — the  question  as  to 
whether  the  killing  of  the  fluke  is  desirable  or  not,  or  as  to  whether 
the  bilharzia  disease  is,  strictly  speaking,  one  due  to  flukes  or  to 
fluke  eggs,  is  not  material.  Looss  does  not  attack  Joannides's  con- 
clusions that  the  embryos  in  the  fluke  eggs  and  possibly  the  adult' 
flukes,  also,  are  killed  by  salvarsan. 

Conor  (1911)  has  tried  salvarsan  in  one  case  of  bilharziasis  and 
found  it  inefficacious.  Eggs  containing  living  miracidia  were  found 
in  the  patient's  urine  every  day  but  one  for  a  month  after  the 
treatment. 

Fiillebom  and  Werner  (1912)  have  also  tried  salvarsan  in  a  case 
of  bilharziasis,  with  the  same  negative  result. 

Day  and  Richards  (1912)  have  criticized  Joannides's  findings,  and 
report  three  cases  in  which  salvarsan  was  administered  with  no  effect 
on  the  passage  of  living  ova  or,  in  two  cases  examined,  on  the 
eosinophilia. 

A  summary  of  the  foregoing  papers  on  the  treatment  of  hepatic 
distomatiasis  shows  the  following: 

The  administration  of  anthelmintics  has  been  declared  effective  by 
Grassi  and  Calandruccio  as  a  result  of  experiments  (number  not 
given)  followed  by  fecal  examination  and  post-mortem  (male  fern)  ; 
by  Perroncito  after  three  experiment  cases  followed  by  fecal  ex- 
amination and  post-mortem  (male  fern)  ;  by  Floris  after  experiments 
(number  not  given)  in  which  no  autopsies  or  subsequent  fecal  ex- 
aminations showing  absence  of  eggs  are  noted  (carbon  bisulphid)  ; 
by  Alessandrini  after  two  experiment  cases  followed  by  autopsy 
(male  fern)  ;  by  Borini  after  experiments  (number  not  given)  in 
which  no  autopsies  or  subsequent  fecal  examinations  showing  absence 
of  eggs  are  noted  (male  fern  and  thymol)  ;  and  by  Railliet,  Moussu, 
and  Henry  after  nine  experiment  cases,  four  other  animals  being 
used  as  checks,  followed  by  autopsy  (male  fern).  This  is  a  total  of 
14  detailed  experiments  and  2  other  sets  of  tests  with  the  number  of 
animals  not  given.  Romagnoli's  treatment  is  omitted  from  con- 
sideration in  this  summary,  as  no  claim  has  been  made  that  it  affects 
parasites  already  established  in  the  host. 

In  the  case  of  venal  distomatiasis,  male  fern  has  been  commended 
as  being* efficacious,  with  no  data  found  by  us  on  casual  examination 


16  ACTION   OF   ANTHELMINTICS   ON    PARASITES. 

of  the  literature  as  to  autopsy  showing  that  the  death  of  the  fluke 
actually  follows  the  administration  of  the  male  fern.  Salvarsan  has 
been  commended  on  the  basis  of  a  cessation  of  symptoms  following  its 
administration  in  eight  cases  of  bilharziasis,  and  opposed  on  the  find- 
ings in  five  cases  in  which  its  administration  was  without  effect. 
Looss  questions  the  benefits  of  salvarsan  as  regards  the  organic 
lesions  due  to  tlie  parasite,  while  the  other  writers  take  exception  to 
Joannides's  findings  as  not  conforming  to  other  knoAvn  facts. 

AUTHORS'    EXPERIMENTS. 

Being  engaged  in  a  study  of  tapewonn  disease  of  sheep,  due  to 
Thysanosoma  actinioides,  the  authors  have  taken  advantage  of  oppor- 
tunities to  test  carbon  bisulphid  and  male  fern  as  remedies  for  this 
disease.  At  the  request  of  a  sheep  owner  we  also  tested  a  certain 
proprietar}'^  remedy.  This  remedy  was  found  on  analysis  by  the 
Biochemic  Division  of  the  Bureau  of  Animal  Industry  to  consist  of 
49  per  cent  ferrous  sulphate,  13  per  cent  arsenious  oxid,  8  per  cent 
oxids  of  calcium,  potassiimi,  silicon,  and  magnesium^  and  29  per  cent 
organic  matter,  nature  not  determined  but  not  containing  santonin, 
or  any  other  vegetable  alkaloid. 

Tests  of  carbon  bisulphid  were  made  by  the  junior  author  at  the 
ranch  of  Mr.  Wells,  near  Resolis^  Colo.,  in  July,  1911.  A  Mexican, 
herder  at  one  camp  was  instructed  to  cut  out  six  sheep,  picking  the 
poorest  and  weakest  as  being  the  most  likely  victims  of  thysano- 
somiasis.  Events  proved  that  some  of  the  sheep  selected  were  really" 
too  sick  for  the  experiment. 

The  experiments  were  as  follows: 

1.  Administered  6  grams  of  carbou  bisulphid  in  capsule  to  a  sheep.  Sheep 
crushed  one  or  two  capsules  and  seemed  greatly  distressed  thereby.  Repeated- 
dose  after  30-hour  interval.  Sheep  found  dead  the  next  day.  Post-mortem 
showed  appearances  similar  to  those  of  hemorrhagic  septicemia.  A  number  of 
live  bile-staiuetl  Thysanosom<i  found  in  the  enlarged  bile  duct^  and  a  number 
of  others  in  the  duodenum.  One  specimen  of  Thysanosoma  was  found  with  the 
head  in  the  fourth  stomach  and  the  rest  of  the  worm  in  the  third  stomach; 
this  might  have  been  due  to  post-mortem  wandering  or  to  a  reverse  peristalsis. 
Two  specimens  of  Ci/sticcrcus  tcnuicoUis  were  found  adhering  to  the  liver  and 
one  to  the  duodenum.  The  fluid  content  of  the  cysticerci  was  stained  with 
blood.  Death  was  perhaps  hastened  by  the  administration  of  the  carboa 
bisulphid.  Two  doses  of  6  grams  each  had  not  killed  the  tapeworms  in  this 
case. 

2.  Administered  6  grams  of  carbon  bisulphid  in  capsule.  Repeated  dose 
after  30-hour  interval.  Sheep  found  dead  the  next  day.  Post-mortem  showed 
appearances  similar  to  those  of  hemorrhagic  septicemia  ;  death  perhaps  hastened 
by  the  administration  of  the  carbon  bisulphid.  There  were  no  tapeworms  any- 
where, and  no  lesions,  such  as  thickened  and  enlarged  bile  and  pancreatic  ducts, 
to  show  that  there  had  been  any  tapeworms. 

3.  Administered  6  grams  of  carbon  bisulphid  in  capsule.  Repeated  dose 
after  30-hour  interval.     Sheep  found  dead  the  next  day.    Post-mortem  showed 


AUTHORS     EXPERIMENTS.  17 

appearances  similar  to  those  of  liemorrhagic  septicemia.  Deatli  was  perhaps 
hastened  by  the  administration  of  carbon  bisulphid.  No  Thysanosoma  or  lesions 
attributable  to  this  worm  were  found. 

4.  Administered  6  grams  of  carbon  bisulphid  in  capsule.  Fifty  hours  later 
administered  4.5  grams  of  cai'bon  bisulphid  and  repeated  this  dose  24  hours 
later.  Killed  the  sheep  20  hours  afterwards.  No  tapeworms  were  found  on 
autopsy,  but  the  gall  ducts  were  thickened  and  enlarged,  as  was  also  the 
pancreatic  duct,  probably  the  result  of  former  infestation  with  Thysanosoma. 
No  worms  had  been  found,  however,  in  the  feces  of  this  or  any  of  the  other 
sheep. 

5.  Administered  6  grams  of  carbon  bisulphid  in  capsule.  Fifty  hours  later 
administered  3.5  grams  of  carbon  bisulphid  and  repeated  this  dose  24  hours 
later.  Killed  the  sheep  20  hours  afterwards.  No  tapeworms  were  found  on 
autopsy. 

6.  Administered  6  grams  of  carbon  bisulphid  in  capsule.  Forty-eight  hours 
later  sheep  was  down,  with  a  respiration  rate  of  210.  Sheep  found  dead  24 
hours  later.  No  evidences  of  the  efficacy  of  the  drug — that  is,  dead  specimens 
of  Thysanosoma — were  found.     Other  notes  regarding  this  autopsy  lost. 

A  summary  of  the  above  experiments  shows  that  sheep  No.  1  had 
live  tapeworms  in  the  liver  and  intestines  after  receiving  two  doses 
of  6  grams  each  of  carbon  bisulphid  on  two  successive  days;  that 
Nos.  2  and  3  after  the  same  treatment  had  no  tapeworms  or  lesions 
indicating  their  presence ;  and  that  Nos.  4,  5,  and  6  showed  no  dead 
tapeworms  on  autopsy.  As  stated  before,  no  tapeworms  were  found 
in  the  feces  of  any  of  these  sheep.  These  experiments  were  incon- 
clusive, but  they  point  to  the  inefficacy  of  carbon  bisulphid  in  that 
where  tapeworms  were  found,  as  they  were  in  one  case,  after  12 
grams  of  carbon  bisulphid  had  been  administered,  the  tapeworms 
were  alive. 

It  should  be  noted  in  this  connection,  as  a  matter  of  passing  inter- 
est, that  no  stomach  worms  were  found  in  these  sheep  on  post-mortem. 

The  next  set  of  experiments  was  made  by  both  of  us  at  Mr.  Wells's 
ranch  later  in  July.  This  time  four  sheep,  selected  as  probably  suffer- 
ing from  Thysanosoma  infection,  were  used  to  test  the  ethereal  extract 
of  male  fern,  and  two  sheep  in  good  condition  were  used  to  test  the 
proprietary  medicine  previously  referred  to.  The  experiments  were 
as  follows: 

Sheep  Nos.  1  and  2  were  given  two  tablets  each  of  the  proprietaiy 
medicine,  according  to  the  directions  furnished  with  the  medicine. 
No.  1  was  killed  24  hours  later.  A  number  of  T'hysanoso7)ui  were 
found  in  the  gall  bladder  and  intestine,  and  ricpmonchus  contortvs 
and  Ostertagia  bullosa  in  the  fourth  stomach.  All  the  worms  were 
alive,  although  the  advertisement  of  the  remedy  claimed  that  the 
dose  given  would  kill  any  worm  in  the  digestive  tract.  No.  2  was 
killed  48  hours  after  receiving  the  dose.  Specimens  of  Thysanosoma 
were  found  in  the  gall  ducts,  two  in  the  pancreatic  duct,  and  a  num- 


18  ACTION   OF   ANTHELMINTICS   ON   PARASITES. 

ber  in  the  intestine;  HcBmonchus  and  Ostertagia  in  the  stomach. 
All  the  worms  were  alive. 

The  analysis,  already  given,  of  this  medicine,  indicated  that  it  is 
practicall)^  inert  as  a  vermifuge  and  that  any  improvement  following 
its  use  would  be  attributable  to  the  tonics  contained  in  it.  The  nega- 
tive results  with  this  medicine  were  precisely  what  might  be  expected. 
At  a  time  when  parasitologists  in  practical  work  are  not  aware  of 
adequate  remedies  for  all  kinds  of  worms,  and  especially  of  any  one 
remedy  which  is  efficacious  against  all  kinds  of  worms,  it  is  unlikely 
that  the  manufacturers  of  proprietary  medicines  will  have  this 
information. 

In  the  male-fern  experiment,  sheep  Nos.  3,  4,  5,  and  6  were  given 
9  c.  c.  of  the  ethereal  extract  thoroughly  mixed  with  25  c.  c.  of 
linseed  oil — the  dose  recommended  by  Railliet,  Moussu,  and  Henry — 
in  the  morning  of  four  successive  days.  They  were  killed  the 
afternoon  of  the  fourth  day.  No.  3  had  one  dead  and  partly  digested 
Thysanosoma  in  the  gall  bladder;  No.  4  had  one  live  ThysaiwsoTna 
in  the  gall  duct  and  one  live  one  in  the  pancreatic  duct ;  Nos.  5  and  6 
had  no  tapeworms.  No  Hcemonchus  was  found  in  smy.  Live  Oster- 
tagia were  found  in  Nos.  1,  2,  and  3.  All  of  the  sheep  had  some 
signs  of  pneumonia,  a  marked  retention  of  urine,  with  a  slight  cys- 
titis, due  apparently  to  the  male  fern.  Considerable  purging 
occurred  during  the  last  two  days,  which  is  attributable  to  the  linseed 
oil.     No  tapeworms  were  found  in  the  feces. 

The  finding  of  a  dead  Thysanosoma  in  the  gall  bladder  of  No.  1 
is  a  fact  pointing  to  a  possible  efficacy  of  the  male  fern ;  the  presence 
of  live  Thysanosoma  in  No.  2  rather  offsets  this. 

As  the  experiments  were  not  conclusive,  we  repeated  them  later  on 
the  ranch  of  Mr.  Kennedy,  near  Amo,  Colo.  Five  sheep  were  selected, 
one  of  them  being  used  as  a  check.  Four  sheep  were  each  dosed  with 
6  c.  c.  of  ethereal  extract  of  male  fern  thoroughly  mixed  with  25  c.  c 
of  linseed  oil,  on  four  successive  days.  The  sheep  were  killed  on  the 
fifth  day.    Autopsy  findings  were  as  follows: 

1.  Twelve  Thysanosoma  in  gall  ducts  and  duodenum  and  2  Strongyloides 
papillosus  in  intestine.    No  Hcemonchus. 

2.  Twelve  Thysanosoma  in  duodenum,  1  in  common  bile  duct,  4  in  biliary 
ducts,  1  in  gall  bladder,  and  1  in  pancreatic  duct,  a  total  of  19 ;  4  Hwmonehus 
and  2  Ostertagia  in  fourth  stomach. 

3.  Five  Thysanosoma  in  duodenum,  1  in  gall  bladder,  and  3  in  bile  ducts,  a 
total  of  9 ;  158  Hwm/mchus  in  fourth  stomach  and  10  Nem^itodirus  filicolHs  in 
intestine. 

4.  Seven  Thysanosoma  in  duodenum  and  5  in  gall  ducts,  a  total  of  12;  a  few 
Hcemonchus  and  about  20  Ostertagia  in  fourth  stomach. 

5.  Check  animal.  Two  Thysanosoma  in  the  gall  ducts;  a  few  Htpmonchua 
and  Ostertagia  in  fourth  stomach  and  3  Strongyloides  in  intestine. 

The  Thysanosoma  were  all  alive,  as  were  the  nematodes. 


GENERAL   SUMMARY   AND   CRITICISM.  19 

It  appears  from  these  experiments  that  male  fern  as  administered 
is  not  efficacious  against  thysanosomiasis.  While  the  negative  find- 
ings of  the  former  experience  are  inconclusive,  the  findings  in  this 
case  are  fairly  conclusive.  The  failure  of  the  medicine  to  exert  any 
effect  on  four  infected  sheep  indicates  that  male  fern  is  not  a  remedy 
which  could  be  recommended  in  thysanosomiasis. 

GENERAL  SUMMARY  AND  CRITICISM. 

It  appears  from  the  foregoing  that  anthelmintics  have  been 
claimed  to  be  efficacious  in  8  cases  of  human  somatic  t.^eniasis  (male 
fern) ;  inefficacious  in  8  cases  of  somatic  taeniasis  in  the  lower  ani- 
mals (male  fern)  ;  inefficacious  in  at  least  6  cases  of  intestinal  and 
extraintestinal  thysanosomiasis  (carbon  bisulphid  and  male  fern) ; 
efficacious  in  over  14  cases  of  hepatic  distomatiasis  (carbon  bisul- 
phid and  male  fern)  ;  efficacious  in  8  cases  of  venal  distomatiasis 
(salvarsan) ;  inefficacious  in  5  cases  of  venal  distomatiasis  (salvar- 
san) ;  and  efficacious  or  inefficacious,  according  to  various  authors,  in 
an  indefinite  number  of  cases  of  venal  distomatiasis  (male  fern). 

While  the  figures  in  the  above  paragraph  are  preponderantly  in 
favor  of  the  efficacy  of  anthelmintics  against  somatic  helminthiasis, 
it  should  be  borne  in  mind  that  there  is  much  more  likelihood  of  cases 
being  published  where  the  administration  of  a  medicine  is  followed 
by  apparent  cure  of  disease  than  where  it  is  followed  by  evident 
failure  to  cure.  Further  objections  to  the  figures  as  they  stand  are 
based  on  a  critical  examination  of  the  cases.  This  criticism  may  be 
summarized  as  follows: 

Ziirn's  experiments  are  entirely  indefinite  and  lacking  in  detailed 
statement.  In  Feletti's  cases  one  patient  died  in  spite  of  treatment 
and  there  was  no  autopsy,  and  in  the  other  cases  the  possibility  of 
spontaneous  degeneration  of  the  cysticerci,  a  not  uncommon  thing, 
is  not  excluded.  De  Kenzi's  cases,  as  we  have  already  stated,  have 
been  criticized  by  Hall  (1909)  as  open  to  suspicion  of  error  as 
regards  diagnosis  and  the  connection  between  the  disease,  the  treat- 
ment, and  the  cure.  Dianoux's  case  is  open  to  much  the  same  criti- 
cism as  those  of  De  Renzi.  Granting  that  the  diagnosis  was  correct 
(as  it  apparently  was  in  this  case),  the  possibility  of  spontaneous 
degeneration  of  the  parasites  is  not  excluded,  and  it  is  not  safe  to 
conclude  that  their  disappearance  was  due  to  the  treatment.  At  least 
one  of  Hall's  cases  was  not  at  all  conclusive.  None  of  the  cases  deal- 
ing with  distomatiasis  specifically  eliminate  the  possibility  of  the 
natural  death  and  spontaneous  evacuation  of  the  flukes,  the  usual 
ending  of  the  yearly  life  cycle,  although  the  use  of  check  animals^ 
where  such  checks  were  used,  probably  meets  this  objection.  Per- 
roncito's  cases  show  that  on  the  basis  of  fecal  examination  the  flukes 
apparently  were  not  killed  in  two  cases  out  of  three.     Floris  and 


20  ACTIOiSr   OF   ANTHELMINTICS   ON   PARASITES. 

Borini  cite  no  post-mortem  findings  or  final  negative  fecal  examina- 
tions in  support  of  their  statements.  Among  the  cases  reported  by 
Railliet,  Moussu,  and  Henry,  autopsy  showed  that  Fasciola  hepatica 
in  four  cases  and  Dicroccelium  lanceatum  in  all  cases  had  survived 
the  full  dose  advocated  by  them.  None  of  Joannides's  cases  were 
followed  by  post-mortem  examination;  and,  so  far  as  case  records 
are  available,  no  cases  of  bilharziasis  treated  by  male  fern  have  been 
followed  by  post-mortem  examination  to  ascertain  whether  the  ad- 
ministration of  the  male  fern  had  resulted  in  the  death  of  the  flukes. 
In  spite  of  these  objections,  the  total  evidence  collected  here  indi- 
cates that  further  work  along  this  line  is  necessary  and  desirable. 
It  is  possible  that  the  common  opinion  that  medicines  administered 
per  orem  or  subcutaneously  can  not  be  successfully  used  against 
metazoan  parasites  outside  of  the  digestive  tract,  that  the  higher 
orders  of  parasites  can  not  be  killed  by  a  selective  action  of  drugs 
without  injury  to  the  host  animal  in  whose  tissues  they  are  located, 
may  be  erroneous.  Improved  technic  and  better  medicines  have 
marked  great  advance  in  the  treatment  of  protozoan  and  bacterial 
diseases.  Similar  improvements  have  led  to  greater  success  in  the 
treatment  of  intestinal  helminthiasis.  May  not  careful  experiment 
lead  to  the  same  results  in  the  treatment  of  somatic  and  extra- 
intestinal helminthiasis?  The  subject  is  worth  investigating.  The 
location  of  metazoan  parasites  often  makes  surgical  treatment  im- 
possible, dangerous,  or  unprofitable.  Adequate  methods  of  medici- 
nal treatment  would  have  great  medical  and  economic  value  as  well 
as  scientific  interest.  The  present  state  of  our  knowledge  does  not 
warrant  any  conclusion  other  than  this,  that  a  great  amount  of  addi- 
tional work  is  necessary  and  desirable. 

BIBLIOGRAPHY.^ 

Alessandrini,  Giulio. 

1908. — Contributo  alio  studio  delle  malattie  parassitarie  delle  pecore  <Boll. 
Soc.  zool.  ital.,  Roma,  v.  17,  2.  s.,  v.  9  (11-12),  pp.  392-400,  1  table.     [W.] 

BOBINI,  Agostino. 

1911. — La  distomatosi  e  sua  cura  <Gazz.  d.  osp.,  Milano,  v.  32  (143),  28 
nov.,  pp.  1515-1516.     [W".] 

CJONOB,  A. 

1911.— Bilharziose  et  606  <Bull.  Soc.  de  path,  exot.  Par.,  v.  4  (1),  11  Jan., 
pp.  45-47.     [W.] 

CtTBTiCE,  Cooper. 

1889a. — Tapeworm  disease  of  sheep  of  the  western  plains  <4th  &  5th  Ann. 

Rep.  Bureau  Animal  Indust.,  U.   S.  Dept.  Agric,  Wash.    (1887-88),  pp. 

167-186,  pis.  1-2,  figs.  1-15.     [W".] 
1890c.— The  animal  parasites  of  sheep.     222  pp.,  36  pis.     8°.     (U.  S.  Dept. 

Agric.)     Washington.     [W".] 

iThls  bibliography  is  prepared  in  the  style  used  in  Bulletin  39  of  this  bureau,  Index- 
Catalogue  of  Medical  and  Veterinary  Zoology. 


BIBLIOGRAPHY.  21 

Day,  H.  B.  ;  &  Richards,  Owen. 

1912. — The  treatment  of  bilharziasis  by  salvarsan  <Lancet,  Lond.   (4626), 
V.  182,  V.  1  (17),  Apr.  27,  pp.  1126-1127.     [W",  W™.] 
Dtvt,  F. 

1911. — Greffe  hydatique  et  foug^re  male  <Compt.  rend.  Soc.  de  biol.,  Par., 
V.  71  (31),  17  nov.,  pp.  420-421.     [W.] 
DiANocx.     [Dr.] 

1909. — Cysticerques  et  foug&re  male  <Gaz.  m§d.  de  Nantes,  v.  27  (49), 
4  d6c.,  pp.  1025-1029.     [W".] 

F^ETTI,   RaIMONDO. 

1894c. — La  cure  de  la  cysticercose  avec  la  foug&re  male  <Mercredi  mM., 
Par.  [V.  5]   (35),  29  aoQt,  pp.  417^18.     [W".] 
Flobis,  Rtjdolph. 

1907. — ^A  sz6nk6neg  alkalmazjlsa  a  m4telyk6r  ellen  <Allat.  lapok,  Budapest, 

V.  30  (45),  nov.  9,  p.  544.     [WM 
1908.— Schwefelkohlenstoff  gegen  distomatosis.     [Abstract  of  1907]   <Berl. 

thierilrztl.  Wchnschr.  (29),  16.  Juli,  p.  518.     [W.] 
1908. — Carboneum  sulphuratum  in  the  treatment  of  distomatosis.     [Abstract 
of  1907  <Am.  Vet.  Rev.,  N.  Y.,  v.  34  (2),  Nov.,  pp.  242-243.     [W.] 
FCtlebobn,  F.  ;  &  Werner  [Dr.]. 

1912. — Ueber  Salvarsanwirkung  bei  Bilharziose  nebst  Bemerkungen  uber 
das  Ausschliipfen  der  Miracidien  <Deutsche  med.  Wchnschr.,  Leipz.,  v. 
38  (8),  22.  Feb.,  pp.  351-352,  figs.  1-2.     [W\\ 
Gbassi,  Giovanni  Battista  ;  &  Calandbuccio,  Salvatore. 

(1884b). — Intorno  ad  una  malattia  parassitaria  (cachessia  Ittero-verminosa 
•    o  cachessia  acquosa  o  marciaja)  <Agric.  calabro  siculo,  Girgenti,  v.  9  (11). 
1885a. — Idem  <Atti  Accad.  Gioenia  di  sc.  nat.  in  Catania,  3.  s.,  v.  18,  pp. 
22^-234.     [W'.] 
Gbenside,  F.  G.     [V.  S.] 

1884a. — Tapeworm  in  lambs  <9.  Ann.  Rep.  Ontario  Agric.  Coll.  &  Exper. 
Farm,  Toronto  (1883),  pp.  200-203.     [MS.  dated  June  25,  1883.] '    [WM 
Halt.,  Maubice  C. 

1909. — A  discussion  of  De  Renzi's  treatment  of  somatic  taeniasis  with  male 
fern,  and  some  tests  of  the  treatment  in  gid.    <Am.  Vet.  Rev,,  N.  Y.,  v.  36 
(3),  Dec.,  pp.  328-337.     [W».] 
JoANNiDfes,  Nicolas  Z.   [Dr.] 

1911. — Die  Wirkung  des  Salvarsans  auf  die  Bilharzia   <Deutsche  med. 
Wchnschr.,  Leipz.,  v.  37  (34),  24.  Aug.,  p.  1551.     [W.] 
Looss,  A.  [Ph.  D.] 

1912. — Ueber  die  sogenannte  Heilung  der   Bllharziosis  durch    Salvarsan 
<Deutsche  med.  Wchnschr.,  v.  38  (2),  11.  Jan.,  p.  70.     [WM 
Milleb,  Fbank  H.  [D.  V.  S.,  Vet.,  Westminster  Kennel  Club,  New  York.] 

1904a. — Iloemorrhagic  colitis  of  the  dog  due  to  infection  with  the  Tricho- 
ccphalus  depressiusculus.     (True  whip  worm)    <Am.  Vet    Rev.,  N.  Y., 
V.  28  (8),  Nov.,  pp.  722-729,  1  pi.,  3  figs.     [W%  W™.] 
Motrssu,  G. 

1910. — Traltemeut  des  maladies  a  cysticerques  par  Textralt  6th^r6  de 
foug&re  male  <Compt.  rend.  Soc.  de  biol.,  Par.,  v.  08  (14),  29  avril, 
pp.  720-722  [W,  WM 

PfiBICAtJD,   HeNBI. 

1908. — Du  traitement  de  la  distomatose  <Progr&s  v6t.,  Agen,  an.  21,  n.  a, 
V.  28  (23),  10  dfc,  pp.  873-880.     [W.] 


22  ACTION   OF  ANTHELMINTICS   ON   PARASITES. 

Pebboncito,  Edoardo. 

18S5c. — Straordinario  numero  di  distomi  nel  fegato  di  una  pecora  affetta 

da  cachessia  ittero-verminosa  e  I'azione  mortale  sopra  di  essi  dell'estratto 

etereo  di  felce  maschio  < Medico  vet.,  Torino,  v.  32    (1),  geunaio,  pp. 

14-16.      [W".] 
18S6f. — Sulla  cachessia  ittero-verminosa.     Studi  e  considerazioni  <  Ann.  r. 

Accad.  d'agric.  di  Torino  (1885),  v.  28,  pp.  83-96,  1  pi.,  figs.  1-3.     [W\] 
Peeroncito,  Edoardo  ;  &  Bosso,  G. 

1894a. — Experiences  sur  la   resistance  vitale  des  larves  d'oestre   (Gastro- 

philus   equi).      [Read   before   Cong,    internat.    d'hyg.    et   de   d6mog.   de 

Budapest,  8  sept.]     <Rec.  de  med.  vet.,  Par.,  v.  71,  8.  s.,  v.  1  (21),  15  nov., 

pp.  657-665.     [W%  W".] 
Powers,  Ray  M.  [D.  V.  S.] 

1909. — Stomach  worm  disease  of  sheep  and  j'oung  cattle  <Bull.  142,  South 

Carolina  Agric.   Exper.   Station,   Clemson  Agric.   Coll.,  Columbia,   S.   C. 

Mar.,  pp.  1-19.     [W.] 
Railliet,  a.  ;  Moussu,  G. ;  &  Henry,  A, 

1911a. — Essais  de  traitement  de  la  distomatose  <Compt.  rend.  Soc.  de  biol.. 

Par.,  V.  70  (11)  24  mars  pp.  427-429.     [W.] 
1911b. — Essais  sur  la  prophylaxie  et  le  traitement  de  la  distomatose  <Rec. 

de  mM.  vet.,  Par.,  v.  88  (7),  15  avril,  pp.  232-238.     [W».] 
1911c. — Recherches  sur  le  traitement  de  la  distomatose  du  mouton  <Compt. 

rend.  Acad.  d.  sc.,  Par.,  v.  152  (17),  24  avril,  pp.  1125-1127.     [WM 
1911d.— Idem  <Rec.  de  m6d.   v6t..  Par.,  v.  88    (9),  15  mai,  pp.  283-289. 

[W.] 
De  Renzi.     [Dr.] 

1908. — Behandlung  des   Cysticercvs  und  Echinococcus  mit  Extract  fllicis 

mar.  aether  <Berl.  klin.  Wchnschr.,  v.  45  (50),  14.  Dec,  pp.  2216-2217. 

[WM 
1909. — L'extrait  ethere  de  foug^re  male  dans  le  traitement  de  la  cysticer- 

cose  c^r^brale  et  de  I'Schinococcose  hepatique.     [Abstract  of  1908,  by 

Railliet]  <Rec.  de  m6d.  v6t..  Par.,  v.  86  (5),  15  mars,  p.  185.     [W%  W"".] 
ROMAGNOLI,  M.    [Dr.] 

(1903a).— [?]  <Mod.  zooiatro,  Torino  (4),  25  feb. 

1903b. — Contre  la  distomatose  du  mouton.     [Abstract  of  1903a,  by  Mathls] 

<J.  de  med.  v6t  et  zootech.,  Lyon,  v.  54,  5.  s.,  v.  7,  31  mal,  p.  301.     [W", 

W".] 
1903c. — Salol  In  hepatic  distomatoses.     [Abstract  of  1903a,  by  A.  Liautard] 

<Am.  Vet.  Rev.,  N.  Y.,  v.  27  (3),  June,  p.  245.     [W%  W",  W".] 
Sandwith,  F.  M.  [M.  D.,  F.  R.  C.  P.,  Prof.  Med.,  Cairo.] 

1909b.— Bilharziasis   <Syst.  Med.    (Allbutt  &  Rolleston),  N.  Y.  &  Lond., 

V.  2,  pt.  2,  pp.  864-883,  figs.  162-167.     [W%  W".] 
Stiles,  Ch[ables]  Wardell. 

1902qq. — Further  investigations  on  verminous  diseases  of  cattle,  sheep,  and 

goats  in  Texas  <  18.  Ann.  Rep.  Bureau  Animal  Indust.,  U.  S.  Dept.  Agric, 

Wash.  (1901),  pp.  223-229.     [W%  W%  Lib.  Stiles.] 
19041. — Illustrated  key  to  the  trematode  parasites  of  man  <Bull.  17,  Hyg. 

Lab.,  U.  S.  Pub.  Health  &  Mar.-IIosp.  Serv.,  Wash.,  Aug.,  pp.  1-66,  figs. 

9-88,  pis.  1-3,  figs.  1-8.     [MS.  dated  Aug.,  1903]     [W*,  W",  W'.] 
Stiles,  Ch[arles]  Wardell;  &  Pfender,  Charles  Alexander. 

1902a. — The  failure  of  thymol  to  expel  whipworms  (Trichuris  depressius- 

cula)   from  dogs  <J.  Comp.  M.  &  Vet.  Arch.,  N.  Y.,  v.  23   (12),  Dec, 

pp.  733-740.     [W,  W".]     [Also  reprint:  W,  W",  Lib.  Stiles.] 


BIBLIOGRAPHY.  23 

Taab,  Gytjla. 

1907a. — A  sz^nkfneg  hatdsa  6s  alkalmazSsa  a  gyomorban,  valamint  a  belek- 
ben  61oskoclo  bogolyj'ilczjlk  6s  orsofgi'gek  elleu  <Anat.  lapok,  Budapest, 
V.  30  (6),  feb.  9,  pp.  65-66.     [W%  W".] 

1907b. — Schwefelkobleiistoff  gegeu  Bremsenlarveu  und  Spulwiirmer.  [Ab- 
stract of  1907a]  <Berl.  tierarztl.  Wclinschr.  (20),  16.  Mai,  p.  406. 
[W,  W".] 

Wessel,  W. 

1901a. — ^Abtreibung  von  Gastruslarven  bei  Fohlen  durch  gchwefelkohlen- 
stofif  <Berl.  tierarztl.  Wclinsclir.  (9),  28.  Feb.,  p.  156.     [W%  W".] 

ZtJBN,  Friedkich  Anton. 

1882a. — Die  Scbniarotzer  auf  und  in  dem  Korper  unserer  Haussiiugetiere, 
sowie  die  durch  erstere  veranlassten  Krankheiten,  deren  Behandlung  und 
Verhiitung.  1.  Theil :  Tierisclie  Parasiten.  2.  Aufl.,  xvi+316  pp.,  4  pis. 
8°.    Weimar.     [W%  W".] 


ADDITIONAL  COPIES  o f  this  publication 
-ii-  may  be  procured  from  the  Superintekd- 
KNT  OK  Documents,  Government  Printing 
OfSce,  Washington ,  D.  C. ,  at  5  cents  per  copy 


A    001  084  321     7 


